Managing weight in patients with type 2 diabetes (most of who have significant overweight or obesity) is always challenging, not least because many medications used to treat diabetes can also promote weight gain.
Now, a paper by Judy Shiau and colleagues from the University of Ottawa, in a paper published in the Canadian Journal of Diabetes, present the results of a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes at 6 months on a low-calorie diet program.
The program (week 1 to week 26) included mandatory weekly group sessions led by a dietitian, behaviour therapist or exercise therapist. All patients received OPTIFAST ®900 as full meal replacements (MR) starting at week 2. Patients consume 4 MR shakes per day for a total of 900 kcal per day, a regimen that is high in proteins (90g/day) and moderate in carbohydrates (67 g/day). Patients with initial body mass indexes (BMIs) of 33 kg/m2 or higher commited to 12 weeks of full MRs, while patients with initial BMIs below 33 started with 6 weeks of full MRs and the option to increase to up to 12 weeks of full MRs. Once patients completed their full MR regimen, there was a 5-week transition period to regular food, typically followed by a maintenance diet, as determined in a one-on- one dietitian counselling session.
As glycemic control improved with weight loss, anti-diabetes medications were adjusted or discontinued, thereby stopping any weight-gain-promoting medications first.
As the authors note,
“At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92% sulfonureas, 87% insulins, 79% thiazolidinediones, 78% alpha-glucosidase inhibitors, 50% meglitinides, 33% dipeptidyl peptidase-4 (DPP-4) inhibitors and 33% metformin. At 6 months, compared with baseline, A1C levels improved significantly and at 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002).”
Thus, this paper shows that, a low-calorie meal replacement program can substantially improve glycemic control and reduce the need for anti-diabetes medications.
Unfortunately, as participants were transitioned to community care at 6 months, little is know about how long these effects last.
Nevertheless, with the increasing availability and use of weight-neutral or even weight-reducing anti-diabetes medications, one may expect that some of these effects can be sustained for relevant periods of time.
Last week I was an invited plenary speaker at the 1st International Diabetes Expert Conclave (IDEC2017) held in Pune, India.
This 3-day event, organised by Drs. Neeta Deshpande (Belgaum), Sanjay Agrawal (Pune) and colleagues, brought together well over 900 physicians from across India for a jam-packed program that covered everything from diabetic food disease and neuropathy to the latest in insulin pumps and devices – all in a uniquely Indian context.
I, of course, was there to speak on obesity, which featured prominently in the program. Topics on obesity ranged from the potential role of gut bugs to bariatric surgery. While Dr. Allison Goldfine, former Director of Clinical Research at the Joslin Diabetes Center in Boston spoke on the latest developments in anti-obesity pharmacotherapy (delivering her talk via Skype), I spoke about obesity as a chronic disease and the need to redefine obesity based on actual indicators of health rather than BMI.
During my visit in Pune, I also had the opportunity to visit with my friend and colleague Dr. Shashank Shah, whose bariatric surgical center in Pune alone performs about 75 to 100 bariatric operations per month – a remarkable number by any standards.
Of course, the overwhelming number of talks were given by Indian faculty (there being only a handful of select invited international faculty at the meeting), and I did come away most impressed by the breadth and depth of knowledge presented by the local speakers.
Diabetes care certainly appears to be in good hands although the sheer number of patients with diabetes (estimated at about 70 million, which I assume to be a rather conservative assessment), would provide a challenge to any health care system.
On the obesity front, things are a lot less rosy, given that (as everywhere else) obesity has yet to receive the same level of professional attention and expertise afforded to diabetes or other chronic diseases.
Thanks again to the organisers for inviting me to this exciting meeting and congratulations on an excellent event that bodes well for the 2nd Conclave planned for 2018.
Just imagine if the question in the title of this post was, “Why would anyone want access to prescription medications for diabetes?” (or heart disease? or lung disease? or arthritis? or, for that matter, cancer?)
Why would anyone even ask that question?
If there is one thing we know for sure about obesity, it is that it behaves just like every other chronic disease.
Once you have it (no matter how or why you got it) – it pretty much becomes a life-long problem. Our bodies are so efficient in defending our body fat, that no matter what diet or exercise program you go on, ultimately, the body wins out and puts the weight back on.
In those few instances where people claim to have “conquered” obesity, you can virtually bet on it, that they are still dealing with keeping the lost weight off every single day of their life – they are not cured, they are just treated! Their risk of putting the weight back on (recidivism) is virtually 100% – it’s usually just a matter of time.
Funnily enough, this is no different from people trying to control any other chronic disease with diet and exercise alone.
Take for e.g. diabetes. It is not that diet and exercise don’t work for diabetes, but the idea that most people can somehow control their diabetes with diet and exercise alone is simply not true. No matter what diet they go on or what exercise program they follow, sooner or later, their blood sugar levels go back up and the problems come back.
You could pretty much say the same for high blood pressure or cholesterol, or pretty much any other chronic health problem (that, in fact, is the very definition of “chronic”).
So why medications for obesity?
Because, like every other chronic disease, medications can help patients achieve long-term treatment goals (of course only as long as they stay on treatment).
Simply put, if the reason people virtually always regain their lost weight (no matter how hard they try to lose it) is simply because of their body’s ability to resist weight loss and promote weight regain, then medications that interfere with the body’s ability to resist weight loss and promote weight regain, will surely make it far more likely for them to not only lose the weight but also keep it off.
Now that we increasingly understand many of the body’s mechanisms to defend against weight loss and promote weight regain (and the body has a whole bag of tricks that you are up against), then pharmacologically blocking these mechanisms makes this a manageable (fair?) fight.
This is by no means easy. Interfering with human physiology always comes at a cost – which is why we need medications that are robustly tested for safety and efficacy (which is why we are here talking about prescription medications and not the nonsense you can buy over the counter in your local drug store or health supplement outlet).
There is of course no guarantee that any one medication will work for or be tolerated by everyone – again, no different from the medications for other chronic diseases (which is why we have so many of them for the same indication).
So who has access to prescription anti-obesity medications in Canada?
Short answer – almost no one.
Thus, in the 2017 Report Card on Access To Obesity Treatment For Adults, released last week at the 5th Canadian Obesity Summit, the less than 20% of Canadians living with obesity (and that is a very generous estimate) have access to the two prescriptions medications approved by Health Canada for long-term treatment of obesity.
Thus, as far a coverage for obesity medications in Canada is concerned,
Neither anti-obesity medication (Xenical® or saxenda®) are listed as a benefit on any provincial/territorial formulary and, therefore, they are not covered under any provincial public drug benefit (or pharmacare) programs.
There may be special-access programs in some provinces that adjudicate coverage for non-formulary medications based on individual case review; however, coverage for anti-obesity medications through these programs are not guaranteed and are, in fact, rare.
Anti-obesity medications are not covered in any federal public drug benefit programs.
Again one must ask, what will it take for governments, employers, and payers to stop discriminating against Canadians living with obesity in our healthcare system?
Disclaimer: I have received honoraria for speaking and consulting for companies that make anti-obesity medications
Every single guideline on obesity management emphasises the importance of interdisciplinary obesity management by a team that not only consists of a physician and a dietitian but also includes psychologists, exercise specialists, social workers, and other health professionals as deemed necessary.
As is evident from the evident from the 2017 Report Card on Access To Obesity Treatment For Adults, released last week at the 5th Canadian Obesity Summit, the overwhelming majority of Canadians living with obesity have no access to anything that even comes close.
Thus, the report finds that
Among the health services provided at the primary care level for obesity management, dietitian services are most commonly available.
Access to exercise professionals, such as exercise physiologists and kinesiologists, at the primary care level is limited throughout Canada.
Access to mental health support and cognitive behavioural therapy for obesity management at the primary care level is also limited throughout Canada. bariatric surgery programs often have a psychologist or a social worker that offers mental health support and cognitive behavioural therapy to patients on the bariatric surgery route, but the availability of these supports outside of these programs is scarce.
Centres where bariatric surgery is conducted also have inter- disciplinary teams that work within the bariatric surgical programs and provide support for patients on the surgical route.
Alberta and ontario have provincial programs with dedicated bariatric specialty clinics that offer physician-supervised medical programs with interdisciplinary teams for obesity management.
Interdisciplinary teams for obesity management outside of the bariatric surgical programs are available in one out of five regional health authorities (RHa) in british Columbia, one out of 18 RHas in Québec, one out of two RHas in new brunswick and one out of four RHas in newfoundland and labrador.
Among the territories, only yukon has a program with an interdisciplinary team focusing on obesity management in adults.
I hardly need to remind readers, that this is in stark contrast to the resources and teams available to patients with diabetes, heart disease, lung disease, or any other common chronic disease, that are regularly available in virtually every health jurisdiction across the country (not to say that they are perfect or sufficient – but at least there is some level of service available).
I understand that our current obesity treatments are extremely limited (at least when effectiveness is measured in terms of weight loss). But even if access to these resources could simply help stabilise and prevent further weight gain (progression) and perhaps improve overall health and well-being, surely Canadians living with obesity should deserve no less that people living with any other chronic disease.
There is simply no excuse for treating Canadians living with obesity as second-class citizens in our publicly funded healthcare system.
Since the introduction of SGLT-2 inhibitors (“gliflozins” or “glucoretics), as an insulin-independent treatment for type 2 diabetes, that works by blocking glucose reabsorbtion in the kidney resulting in loss of glucose (and calories) through the kidney, much has been written about the (albeit modest) weight loss associated with this treatment.
Several studies have documented that the weight loss leads to a change in body composition with an often significant reduction in fat mass.
Now, Giuseppe Daniele and colleagues, in a paper published in Diabetes Care, show that treatment with these compounds may enhance fat oxidation and increase ketone production in patients with type 2 diabetes.
The researchers randomized 18 individuals with type 2 diabetes to dapagliflozin or placebo for two weeks.
As expected, dapagliflozin reduced fasting plasma glucose significantly (from 167 to 128 mg/dL).
It also increased insulin-stimulated glucose disposal (measured by insulin clamp) by 36%, indicating a significant increase in insulin sensitivity.
Compared to baseline, glucose oxidation decreased by about 20%, whereas nonoxidative glucose disposal (glycogen synthesis) increased by almost 50%.
Moreover, dapagliflozin increased lipid oxidation resulting in a four-fold increase in plasma ketone concentration and and a 30% increase in fasting plasma glucagon.
Thus, the authors note that treatment with dapagliflozine improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production.
While this may explain the recent observation of a greater (albeit still rather rare) incidence of ketoacidosis with the use of these compounds, these findings may also explain part of the change in body composition previously noted with SGLT-2 treatment.
While this still does not make SGLT-2 inhibitors “weight-loss drugs”, there appears to be more to the fat loss seen with these compounds than just the urinary excretion of glucose.